Studies in our laboratory have shown that the anti-cancer agent cyclophosphamide is very effective in preventing the growth of syngenic transplants of PARA-7 transformed hamster embryo fibroblast cells. Indeed, chemotherapy appears to be capable of totally eradicating greater than 10 to the 5th power cancer cells. The goal of the proposed experiments is to determine why chemotherapy was successful. There would appear to be two possible explanations. Either the drug by itself is sufficient to destroy the transplant, or the drug acts in concert with host defense mechanisms to eradicate the tumor cells. The direct effect of the activated drug metabolites on the tumor cells will be determined by employing a recently developed biological assay. Serum collected shortly after drug treatment is tested for its capacity to inhibit tumor cell replication in vitro. The same assay will be used to monitor the pharmacokinetics of cyclophosphamide activation under various conditions. Utilizing microcytotoxic assays we will characterize the nature of the hamster's cellular and humoral immune response to the tumor cells, and examine what effect cyclophosphamide has on that response. The contribution of host immunity to tumor cell eradication will be evaluated by carrying out chemotherapeutic experiments in immunosuppressed animals.